Effects of age on neurochemical markers in rodents and the correlation between these markers and behavior as well as genotype have been tested. Young adult and aged Wistar rats were tested in a 12-arm radial maze. To determine if possible age-associated behavioral alterations were correlated with defects in cholinergic, gamma-aminobutyric acid (GABA)-ergic and adrenergic neurons in the cerebral cortex and hippocampus, acitivities of choline acetyltransferase (CAT), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH), presynaptic markers for cholinergic, GABAergic and adrenergic neurons, respectively, were assayed in these brain regions after animals were tested in the maze. Aged rats showed severe behavioral decrements as compared with young rats whereas the only significant neurochemical age effect was an increase in hippocampal TH. Maze performance was positively correlated with hippocampal CAT in aged rats and cortical GAD in young as well as aged rats. Effects of genotype and age on activities of CAT, GAD and TH in the striaatum, hippocampus, cerebral cortex and cerebellum were studied simultaneously in two inbred strains of mice (C57BL/6J and A/J). Regional activities of the three enzymes were altered by age, and the effect of age varied with the genetic strain.